Omega-3 Fatty Acids and Airway Hyperresponsiveness in Asthma

ABSTRACT Despite the progress that has been made in the treatment of asthma, the prevalence and burden of this disease has continued to increase. Exercise is a powerful trigger of asthma symptoms and reversible airflow obstruction and may result in the avoidance of physical activity by patients with asthma, resulting in detrimental consequences to their health. Approximately 90% of patients with asthma are hyperresponsive to exercise and experience exercise-induced bronchoconstriction (EIB). While pharmacologic treatment of asthma is usually highly effective, medications often have significant side-effects or exhibit tachyphylaxis. Alternative therapies for treatment (complementary medicine) that reduce the dose requirements of pharmacologic interventions would be beneficial, and could potentially reduce the public health burden of this disease. There is accumulating evidence that dietary modification has potential to influence the severity of asthma and reduce the prevalence and incidence of this condition. A possible contributing factor to the increased incidence of asthma in Western societies may be the consumption of a proinflammatory diet. In the typical Western diet, 20-to 25-fold more -6 polyunsaturated fatty acids (PUFA) than -3 PUFA are consumed, which causes the release of proinflammatory arachidonic acid metabolites (leukotrienes and prostanoids). This review analyzes the existing literature on -3 PUFA supplementation as a potential modifier of airway hyperresponsiveness in asthma and includes studies concerning the efficacy of -3 PUFA supplementation in EIB. While clinical data evaluating the effect of -3 PUFA supplementation in asthma has been equivocal, it has recently been shown that pharmaceuticalgrade fish oil (-3 PUFA) supplementation reduces airway hyperresponsiveness after exercise, medication use, and proinflammatory mediator generation in nonatopic elite athletes with EIB. These findings are provocative and suggest that dietary -3 PUFA supplementation may be a viable treatment modality and/or adjunct therapy in airway hyperresponsiveness. Further studies are needed to confirm these results and understand their mechanism of action. 106

Air quality and error quantity: pollution and performance in a high-skilled, quality-focused occupation

We provide the first evidence that short-term exposure to air pollution affects the work performance of a group of highly-skilled, quality-focused employees. We repeatedly observe the decision-making of individual professional baseball umpires, quasi-randomly assigned to varying air quality across time and space. Unique characteristics of this setting combined with high-frequency data disentangle effects of multiple pollutants and identify previously under-explored acute effects. We find a 1 ppm increase in 3-hour CO causes an 11.5% increase in the propensity of umpires to make incorrect calls and a 10 mg/m3 increase in 12-hour PM2.5 causes a 2.6% increase. We control carefully for a variety of potential confounders and results are supported by robustness and falsification checks

Imitators of exercise-induced bronchoconstriction

Exercise-induced bronchoconstriction (EIB) is described by transient narrowing of the airways after exercise. It occurs in approximately 10% of the general population, while athletes may show a higher prevalence, especially in cold weather and ice rink athletes. Diagnosis of EIB is often made on the basis of self-reported symptoms without objective lung function tests, however, the presence of EIB can not be accurately determined on the basis of symptoms and may be under-, over-, or misdiagnosed. The goal of this review is to describe other clinical entities that mimic asthma or EIB symptoms and can be confused with EIB

Empirical Legal Studies Before 1940: A Bibliographic Essay

The modern empirical legal studies movement has well-known antecedents in the law and society and law and economics traditions of the latter half of the 20th century. Less well known is the body of empirical research on legal phenomena from the period prior to World War II. This paper is an extensive bibliographic essay that surveys the English language empirical legal research from approximately 1940 and earlier. The essay is arranged around the themes in the research: criminal justice, civil justice (general studies of civil litigation, auto accident litigation and compensation, divorce, small claims, jurisdiction and procedure, civil juries), debt and bankruptcy, banking, appellate courts, legal needs, legal profession (including legal education), and judicial staffing and selection. Accompanying the essay is an extensive bibliography of research articles, books, and reports

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Grade Influences Blood Lactate Kinetics During Cross-Country Skiing

The purpose of this study was to examine the effects of level vs. graded skate skiing on capillary blood lactate (BLa), heart rate (HR), oxygen consumption (V_ O2), and training intensity prescriptions. Eleven Nordic skiers completed 2 submaximal skate roller skiing treadmill protocols during which intensity was increased either by grade (Ginc) or by speed (Sinc). The protocols were compared for prethreshold BLa, HR, and V_ O2 at lactate threshold (LT) and the HR/V_ O2 relationship. Additionally, double-pole (primarily upper body) and skating (arms and legs combined) protocols were used to measure peak V_ O2 and peak HR. Heart rate and V_ O2 at LT were lower during Ginc compared with Sinc (154.9 6 6.8 b min21 vs. 162.0 6 9.1 b min21 and 46.3 6 2.8 ml kg21 min21 vs. 49.1 6 1.6 ml kg21 min21 , respectively, both p , 0.01). Prethreshold BLa and the HR/V_ O2 relationship were not different between the submaximal protocols. V_ O2peak and HRpeak were higher in skating compared with double poling (64.6 6 1.8 ml kg21 min21 vs. 60.3 6 2.8 ml kg21 min21 , 192.6 6 5.8 b min21 vs. 187.8 6 6.7 b min21 , respectively, both p , 0.01). Greater reliance on upper-body musculature during graded skiing and its associated lower aerobic capacity increases BLa when compared with level skiing. The leftward shift in the BLa vs. intensity curve during uphill skiing should be recognized to properly prescribe training intensity as well as interpret laboratory results